A. Murine milk contains, besides caseins and Alpha-lactalbumins another abundant class of protein, the whey-acidic proteins. We first isolated this protein from rat milk and the sequence of the first 20 amino-terminal residues were determined by direct protein sequence analysis. The full sequence of the protein was further derived by isolating a cDNA clone corresponding to rat whey-acidic phosphoprotein and sequencing its DNA. The protein sequence shows following unique features: a) Whey-acidic phosphoproteins contain high content of cysteine, glutamic acid, aspartic acid and serine, but lack tyrosine. Half-cystines appear in unique arrangements and are repeated in two domains of the protein. The arrangement of half-cystines show striking similarities with the arrangement of cysteines in neurophysins and certain type of lectins like Con A and wheat germ agglutinin, b) the second domain has also striking similarities with the second domain of the red sea turtle protease inhibitor. B. We have also isolated a cDNA clone encoding a protein which we have named k-protein. The cDNA derived protein sequence lacks in cysteine and has several potential phosphorylation sites. C. We have isolated the genomic clones corresponding to whey-acidic and k-protein from a bacteriophage Charon 4A/rat partial EcoRi genomic library and established the genomic organization for these genes.